The present invention relates broadly to the treatment of inflammatory bowel diseases in a patient. More particularly, the invention relates to treating a patient having an inflammatory bowel disease condition with Hepatocyte Growth Factor ("HGF").
Chronic Ulcerative Colitis ("CUC") and Crohn's Disease ("CD"), generally referred to as Inflammatory Bowel Disease ("IBD"), are devastating disorders with an unknown etiology. Current medical therapy can control symptomatic exacerbations of IBD, but does not provide a cure. Progress in understanding the pathogenesis of IBD has been slowed by the lack of availability of animal models that exhibit the chronic, spontaneous, relapsing gastrointestinal ("GI") inflammation that is symptomatic of human IBD. Numerous murine and rat experimental models exist that possess some but not all of the features of human IBD.
A study has shown that the introduction of HLA-B27 and human .beta..sub.2 -microglobulin genes into Fisher (F344) rats induces spontaneous chronic GI inflammation. Hammer et al., Cell 63: 1099-1112 (1990). In this model, rats spontaneously develop a chronic inflammatory disease that includes most of the clinical and pathologic features of the B27-associated disorders in humans. The most prevalent site of inflammation in these transgenic rats appears to be localized to the gastro-intestinal tract, and the most persistent finding is diarrhea developing in 100% of the animals at 20 weeks of age. Hammer et al., Cell 63: 1099-1112 (1990); Elson et al., Gastroenterology 109: 1344-1367 (1995). Because it closely approximates the human disease, as will be described in detail below, this transgenic rat model was used to study the therapeutic benefit of HGF as a treatment for IBD.
In a previous application, application Ser. No. 08/932,391, filed on Sep. 17, 1997, herein specifically incorporated by reference, HGF was shown to increase the intestinal absorptive functions and increase the intestinal tissue mass of the small intestine beyond the normal adaptive response in subjects suffering from Short Bowel Syndrome, a surgical resection of the small intestine or other developmental abnormalities of the small intestine. The subject of the present invention relates to the therapeutic benefits of treating subjects with HGF who are suffering from inflammation of the bowel as in IBD.